The Mexican club suffered a heavy defeat, while Boca Juniors overcame Cerro Porteno away from home.
Defending champions River Plate suffered a surprise 2-0 defeat at Independiente del Valle in the first leg of their Copa Libertadores last-16 tie.
After a scoreless opening half in Sangolqui in Ecuador on Thursday, Jose Angulo's 64th-minute opener and Junior Sornoza's stoppage-time penalty sealed the home win for Independiente.
River had only lost one match in the group stages, and that was away from home earlier this month. And its poor away form - just one win in seven games in all competitions - came back to haunt the Argentine giants again.